Research

My research: background, current projects, and perspectives

The responses of organisms to biotic and abiotic changes in their environments is a fascinating topic. Cells and organs can quickly change their metabolism to improve the biotransformation and excretion of toxic and undesired chemicals or to match new cellular energy requirements in response to environmental stressors. Investigating the contrast between coping and failing to respond to such stressors at the biochemical and physiological levels in non-target aquatic organisms has been the main driver of my research career.

Current and previous research

As an early undergraduate researcher in Biological Sciences and during my MSc and PhD in Biochemistry, all at the Federal University of Santa Catarina, my main focus was on the importance of the antioxidant system for organismal health during exposure to pollutants. Many abiotic factors are known to modulate different components of this system, which can be detrimental for cellular homeostasis, especially when its efficiency is further required (i.e. spawning season, embryonic development, multiple stressors). My research demonstrated that zinc modulates the glutathione system of marine mussels, leading to an initial oxidative insult followed by an overall amplification of the antioxidant system and cellular protection. The relationship between the glutathione system and organismal health was further investigated in bivalves exposed to different chemicals with anti- or pro-oxidant activities. Slowing down the recycling of glutathione or thioredoxin in bivalves diminishes the in vivo peroxide clearance rate, suppresses the immune system, and increases organismal susceptibility to additional oxidative stress while overexpressing antioxidants such as glutathione and glutathione peroxidase has opposite effects. I concluded that the glutathione system is a particularly efficient and responsive cellular defense in bivalves against environmental stressors, especially in the gills where it can act as a metabolic barrier against electrophilic substances through absorption, metabolism, and metabolite excretion. These laboratory findings were accompanied by field studies with native or transplanted bivalves and fish from polluted mangroves, rivers, coastal zones, and offshore areas. 

Moving a step further into mechanisms associated with oxidative stress, I became interested in the profile of protein oxidation induced by pollutant exposures. I was able to correlate the oxidation of mitochondrial proteins to its loss of function and integrity in bivalves exposed to zinc oxide nanoparticles. I also identified that the most predominant protein in oysters plasma can be oxidized by metals, pathogens, and chemicals found in urban sewage, which can be used as a promising screening tool for oyster health status. Such oxidation appears to affect the recognition of pathogens by the immune cells, potentially increasing the susceptibility of the animals to diseases. Later, as a component of my postdoctoral work, I investigated how environmental stressors can interfere with energy metabolism during embryonic and larval development of zebrafish (Danio rerio) and Atlantic killifish (Fundulus heteroclitus) as a Research Scientist at Duke University (US). Some of the stressors I have been increasingly interested in include temperature, hypoxia, and ubiquitous pollutants such as plastic particles and polycyclic aromatic hydrocarbons (PAHs). To pursue this line of research I combine both modern and classic techniques. I study whole animal respirometry and organ-specific mitochondrial function analyses using a high-throughput bioenergetic assay (XFe extracellular flux analyzer), zebrafish mitochondrial transgenic reporters and mitochondrial dyes, as well as biochemical assays to determine the efficiency of the citric acid cycle and the activity of mitochondrial protein complexes. I am also interested in cardiovascular health by assessing its development using zebrafish transgenic lines and performing heart rate and morphology measurements. With this approach, I found that nanoplastics can accumulate in the mitochondria during fish development as a result of waterborne exposure or maternal transfer, which was associated with decreased ATP production efficiency, increased mitochondrial content and changes in larval behavior. Nanoplastics appear to also transport co-contaminants such as PAHs into the mitochondria, increasing the effects on mitochondrial respiration what may potentially exacerbate the metabolic cost of exposure to nanoplastics.

Future directions and research goals

My overarching research vision is to understand how organisms respond to environmental challenges at the physiological and molecular levels. More recently, I have been interested in addressing how changes in the mitochondrial metabolism induced by environmental stressors can impact organism physiology and overall health. I would like to develop an integrative research program focusing on some of the following questions:

(i) What are the impacts of plastic pollution to our ecosystems? Can we use fish and bivalves as models to characterize adverse effects associated with the exposure to small plastic particles?

(ii) Can plastic pollution affect reproduction and energy metabolism in aquatic species? And Can it affect multiple generations by targeting the gonads and gametes of exposed adults?

(iii) Can small plastic particles transfer other environmental pollutants sorbed to their surfaces to organs or organelles commonly targeted by plastics in the organisms?

I am also interested in understanding mechanisms associated with cellular defense and animal survival under exposure to environmental stressors. More specifically, I would like to address some of the following questions related to mitochondrial biology and metabolism:

(iv) What is the role of mitochondrial antioxidants and oxidation events in regulating mitochondrial function and metabolism of organisms facing environmental challenges?

(v)What are the long-term physiological consequences of mitochondrial impairment 

Publications

Below is the list of publications, organized by theme or area of interest: plastic pollution, neuroscience, mechanisms of cellular defense to aquatic pollution, and biomonitoring field studies

Effects of plastic pollution

  1. Trevisan R, Uzochukwu D, Di Giulio RT. PAH Sorption to Nanoplastics and the Trojan Horse Effect as Drivers of Mitochondrial Toxicity and PAH Localization in Zebrafish. Front Environ Sci. 2020 July 24; Article 78. doi:10.3389/fenvs.2020.00078
  2. Trevisan R, Voy C, Chen S, Di Giulio RT. Nanoplastics Decrease the Toxicity of a Complex PAH Mixture but Impair Mitochondrial Energy Production in Developing Zebrafish. Environ Sci Technol. 2019 Jul 16;53(14):8405-8415. doi:10.1021/acs.est.9b02003
  3. Pitt JA, Trevisan R, Massarsky A, Kozal JS, Levin ED, Di Giulio RT. Maternal transfer of nanoplastics to offspring in zebrafish (Danio rerio): A case study with nanopolystyrene. Sci Total Environ. 2018 Dec 1;643:324-334. doi:10.1016/j.scitotenv.2018.06.186.
  4. Pitt JA, Kozal JS, Jayasundara N, Massarsky A, Trevisan R, Geitner N, Wiesner M, Levin ED, Di Giulio RT. Uptake, tissue distribution, and toxicity of polystyrene nanoparticles in developing zebrafish (Danio rerio). Aquat Toxicol. 2018 Jan;194:185-194. doi:10.1016/j.aquatox.2017.11.017

Environmental biomonitoring studies

  1. Piazza CE, Mattos JJ, de Toledo-Silva G, Flores-Nunes F, Tadra-Sfeir MZ, Trevisan R, Bittencourt AC, Bícego MC, Taniguchi S, Marques MRF, Dafré AL, Bianchini A, Souza EM, Bainy ACD. Transcriptional effects in the estuarine guppy Poecilia vivipara exposed to sanitary sewage in laboratory and in situ.
  2. Ecotoxicol Environ Saf. 2019 Oct 30;182:109411. doi:10.1016/j.ecoenv.2019.109411
  3. Mello DF, Danielli NM, Curbani F, Pontinha VA, Suhnel S, Castro MAM, Medeiros SC, Wendt NC, Trevisan R, Magalhães ARM,Dafre AL. First evidence of viral and bacterial oyster pathogens in the Brazilian coast.J Fish Dis. 2018 Mar;41(3):559-563. doi:10.1111/jfd.12755
  4. Trevisan R, Flores-Nunes F, Dolores ES, Mattos JJ, Piazza CE, Sasaki ST, Taniguchi S, Montone RC, Bícego MC, Dos Reis IMM, Zacchi FL, Othero BNM, Bastolla CLV, Mello DF, Fraga APM, Wendt N, Toledo-Silva G, Razzera G, Dafre AL, de Melo CMR, Bianchini A, Marques MRF, Bainy ACD. Thiol oxidation of hemolymph proteins in oysters Crassostrea brasiliana as markers of oxidative damage induced by urban sewage exposure. Environ Toxicol Chem. 2017 Jul;36(7):1833-1845. doi: 10.1002/etc.3543
  5. Trevisan R, Uliano-Silva M, Franco JL, Posser T, Hoppe R, Farina M, Bainy AC,Dafre AL. Confinement during field studies may jeopardize antioxidant and physiological responses of Nile tilapia to contaminants. Mar Environ Res. 2013 Oct;91:97-103. doi: 10.1016/j.marenvres.2013.07.005

Cellular defenses and aquatic pollution

  1. Mello DF, Trevisan R, Danielli NM, Dafre AL. Vulnerability of glutathione-depleted Crassostrea gigas oysters to Vibrio species. Mar Environ Res. 2020 Feb;154:104870. doi: 10.1016/j.marenvres.2019.104870
  2. Mello DF, Trevisan R, Rivera N, Geitner NK, Di Giulio RT, Wiesner MR, Hsu-Kim H, Meyer JN. Caveats to the use of MTT, neutral red, Hoechst and Resazurin to measure silver nanoparticle cytotoxicity. Chem Biol Interact. 2020 Jan 5;315:108868. doi: 10.1016/j.cbi.2019.108868
  3. Nunes MEM, Schimith LE, da Costa-Silva DG, Lopes AR, Leandro LP, Martins IK, de Mello RS, Hartmann DD, de Carvalho NR, da Rosa PC, Trevisan R, Di Giulio RT, Posser T, Franco JL. Acute Exposure to Permethrin Modulates Behavioral Functions, Redox, and Bioenergetics Parameters and Induces DNA Damage and Cell Death in Larval Zebrafish. Oxid Med Cell Longev. 2019 Nov 11;2019:9149203. doi:10.1155/2019/9149203.
  4. Abtahi MHS, Trevisan R, Di Giulio R, Murphy CJ, Saleh NB, Vikesland PJ. Implications of Aspect Ratio on the Uptake and 2 Nanotoxicity of Gold Nanomaterials. Nanoimpact. 2019 Feb; 14:100153. doi:10.1016/j.impact.2019.100153
  5. Karmous I, Trevisan R, El Ferjani E, Chaoui A, Sheehan D. Redox biology response in germinating Phaseolus vulgaris seeds exposed to copper: Evidence for differential redox buffering in seedlings and cotyledon. PLoS One. 2017 Oct 5;12(10):e0184396. doi: 10.1371/journal.pone.0184396
  6. Danielli NM, Trevisan R, Mello DF, Fischer K, Deconto VS, Bianchini A, Bainy ACD, Dafre AL. Contrasting effects of a classic Nrf2 activator, tert-butylhydroquinone, on the glutathione-related antioxidant defenses in Pacific oysters, Crassostrea gigas. Mar Environ Res. 2017 Sep;130:142-149. doi: 10.1016/j.marenvres.2017.07.020
  7. Nogueira L, Mello DF, Trevisan R, Garcia D, da Silva Acosta D, Dafre AL, de Almeida EA. Hypoxia effects on oxidative stress and immunocompetence biomarkers in the mussel Perna perna (Mytilidae, Bivalvia). Mar Environ Res. 2017 May;126:109-115. doi: 10.1016/j.marenvres.2017.02.009
  8. Danielli NM, Trevisan R, Mello DF, Fischer K, Deconto VS, da Silva Acosta D, Bianchini A, Bainy AC, Dafre AL. Upregulating Nrf2-dependent antioxidant defenses in Pacific oysters Crassostrea gigas: Investigating the Nrf2/Keap1 pathway in bivalves. Comp Biochem Physiol C Toxicol Pharmacol. 2017 May;195:16-26. doi: 10.1016/j.cbpc.2017.02.004
  9. Piazza RS, Trevisan R, Flores-Nunes F, Toledo-Silva G, Wendt N, Mattos JJ, Lima D, Taniguchi S, Sasaki ST, Mello ÁC, Zacchi FL, Serrano MA, Gomes CH, Bícego MC, Almeida EA, Bainy AC. Exposure to phenanthrene and depuration: Changes on gene transcription, enzymatic activity and lipid peroxidation in gill of scallops Nodipecten nodosus. Aquat Toxicol. 2016 Aug;177:146-55. doi: 10.1016/j.aquatox.2016.05.025
  10. Trevisan R, Mello DF, Delapedra G, Silva DGH, Arl M, Danielli NM, Metian M, Almeida EA, Dafre AL. Gills as a glutathione-dependent metabolic barrier in Pacific oysters Crassostrea gigas: Absorption, metabolism and excretion of a model electrophile. Aquat Toxicol. 2016 Apr;173:105-119. doi: 10.1016/j.aquatox.2016.01.008.
  11. Mello DF, Arl M, Trevisan R, Dafre AL. How important are glutathione and thiol reductases to oyster hemocyte function? Fish Shellfish Immunol. 2015 Oct;46(2):566-72. doi: 10.1016/j.fsi.2015.07.017
  12. Nogueira L, Garcia D, Trevisan R, Sanches AL, da Silva Acosta D, Dafre AL, Oliveira TY, de Almeida EA. Biochemical responses in mussels Perna perna exposed to diesel B5. Chemosphere. 2015 Sep;134:210-6. doi: 10.1016/j.chemosphere.2015.04.034
  13. Trevisan R, Mello DF, Uliano-Silva M, Delapedra G, Arl M, Dafre AL. The biological importance of glutathione peroxidase and peroxiredoxin backup systems in bivalves during peroxide exposure. Mar Environ Res. 2014 Oct;101:81-90. doi: 10.1016/j.marenvres.2014.09.004
  14. Lüchmann KH, Dafre AL, Trevisan R, Craft JA, Meng X, Mattos JJ, Zacchi FL, Dorrington TS, Schroeder DC, Bainy AC. A light in the darkness: new biotransformation genes, antioxidant parameters and tissue-specific responses in oysters exposed to phenanthrene. Aquat Toxicol. 2014 Jul;152:324-34. doi: 10.1016/j.aquatox.2014.04.021
  15. Trevisan R, Delapedra G, Mello DF, Arl M, Schmidt ÉC, Meder F, Monopoli M, Cargnin-Ferreira E, Bouzon ZL, Fisher AS, Sheehan D, Dafre AL. Gills are an initial target of zinc oxide nanoparticles in oysters Crassostrea gigas, leading to mitochondrial disruption and oxidative stress. Aquat Toxicol. 2014 Aug;153:27-38. doi: 10.1016/j.aquatox.2014.03.018
  16. Trevisan R, Flesch S, Mattos JJ, Milani MR, Bainy AC, Dafre AL. Zinc causes acute impairment of glutathione metabolism followed by coordinated antioxidant defenses amplification in gills of brown mussels Perna perna. Comp Biochem Physiol C Toxicol Pharmacol. 2014 Jan;159:22-30. doi: 10.1016/j.cbpc.2013.09.007
  17. Mello DF, de Oliveira ES, Vieira RC, Simoes E, Trevisan R, Dafre AL, Barracco MA. Cellular and transcriptional responses of Crassostrea gigas hemocytes exposed in vitro to brevetoxin (PbTx-2). Mar Drugs. 2012 Mar;10(3):583-97. doi: 10.3390/md10030583.
  18. Trevisan R, Arl M, Sacchet CL, Engel CS, Danielli NM, Mello DF, Brocardo C, Maris AF, Dafre AL. Antioxidant deficit in gills of Pacific oyster (Crassostrea gigas) exposed to chlorodinitrobenzene increases menadione toxicity. Aquat Toxicol. 2012 Feb;108:85-93. doi:10.1016/j.aquatox.2011.09.023
  19. Trevisan R, Mello DF, Fisher AS, Schuwerack PM, Dafre AL, Moody AJ. Selenium in water enhances antioxidant defenses and protects against copper-induced DNA damage in the blue mussel Mytilus edulis. Aquat Toxicol. 2011 Jan 17;101(1):64-71. doi: 10.1016/j.aquatox.2010.09.003
  20. Franco JL, Posser T, Mattos JJ, Sánchez-Chardi A, Trevisan R, Oliveira CS, Carvalho PS, Leal RB, Marques MR, Bainy AC, Dafre AL. Biochemical alterations in juvenile carp (Cyprinus carpio) exposed to zinc: glutathione reductase as a target. Mar Environ Res. 2008 Jul;66(1):88-9. doi:10.1016/j.marenvres.2008.02.031
  21. Franco JL, Trivella DB, Trevisan R, Dinslaken DF, Marques MR, Bainy AC, Dafre AL. Antioxidant status and stress proteins in the gills of the brown mussel Perna perna exposed to zinc. Chem Biol Interact. 2006 Apr 15;160(3):232-40. doi:10.1016/j.cbi.2006.02.002

Neuroscience

  1. Brocardo PS, Budni J, Pavesi E, Franco JL, Uliano-Silva M, Trevisan R, Terenzi MG, Dafre AL, Rodrigues AL. Folic acid administration prevents ouabain-induced hyperlocomotion and alterations in oxidative stress markers in the rat brain. Bipolar Disord. 2010 Jun;12(4):414-24. doi: 10.1111/j.1399-5618.2010.00827.x
  2. Maris AF, Franco JL, Mitozo PA, Paviani G, Borowski C, Trevisan R, Uliano-Silva M, Farina M, Dafre AL. Gender effects of acute malathion or zinc exposure on the antioxidant response of rat hippocampus and cerebral cortex. Basic Clin Pharmacol Toxicol. 2010 Dec;107(6):965-70. doi: 10.1111/j.1742-7843.2010.00614.x
  3. Franco JL, Posser T, Mattos JJ, Trevisan R, Brocardo PS, Rodrigues AL, Leal RB, Farina M, Marques MR, Bainy AC, Dafre AL. Zinc reverses malathion-induced impairment in antioxidant defenses.Toxicol Lett. 2009 Jun 22;187(3):137-43. doi:10.1016/j.toxlet.2009.02.015
  4. Trevisan R, Uliano-Silva M, Pandolfo P, Franco JL, Brocardo PS, Santos AR, Farina M, Rodrigues AL, Takahashi RN, Dafre AL. Antioxidant and acetylcholinesterase response to repeated malathion exposure in rat cerebral cortex and hippocampus. Basic Clin Pharmacol Toxicol. 2008 Apr;102(4):365-9. doi:10.1111/j.1742-7843.2007.00182.x
  5. Franco JL, Posser T, Brocardo PS, Trevisan R, Uliano-Silva M, Gabilan NH, Santos AR, Leal RB, Rodrigues AL, Farina M, Dafre AL. Involvement of glutathione, ERK1/2 phosphorylation and BDNF expression in the antidepressant-like effect of zinc in rats. Behav Brain Res. 2008 Apr 9;188(2):316-23. doi:10.1016/j.bbr.2007.11.012 

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